Antioxidation mechanisms of uric acid

Abstract

One-electron oxidation of uric acid generates the urate radical, which was studied in aqueous solution by pulse radiolysis and oxygen-uptake measurements. Acid-base properties of the uric acid radical were determined, i.e., p£al = 3.1 ± 0.1 and pXa2 = 9.5 ± 0.1. The reaction of the radical with oxygen was too slow to be measured, k < 10~2 dm3 mol-1 s'1. The one-electron-redox potential vs NHE, £7 = 0.59 V, was derived from the pH dependence of the redox potential, which was fitted through the values measured at pH 7 and 8.9 and those previously determined at pH 13. Rapid reactions of uric acid with oxidizing species and peroxy radicals were indicative of uric acid as a possible water-soluble physiological antioxidant. Rapid reaction of uric acid with the guanyl radical indicates that uric acid may also act as a repair agent of oxidative damage to DNA bases.Free-radical processes are increasingly invoked in many deleterious biological effects,1 such as replicative inactivation of DNA,2 mutation,3 carcinogenesis,4 atherosclerosis,5 arthritis,6 and aging.7 The generation of free radicals in biosystems exposed to ionizing radiations2 or in systems undergoing autoxidation5 has been firmly established by numerous direct observations of free radicals and their reactions in appropriate model systems.8 The involvement of free radicals in normal physiology,9 pathophysiology,10 and aging,7 although lacking direct proof, is backed by strong indirect evidence. Direct monitoring of free radicals in vivo is much more complex than detecting their presence in model biosystems,11 which is in any case considerably limited. Consequently, in addition to indirect-measurement approaches in vivo, comparison to model systems is crucial in assessing free-radical processes in biological media. In this work, the energetics, kinetics, and mechanisms of the antioxidant properties of uric acid were investigated by pulse and steady-state radiolysis in model aqueous solutions.Various sulfhydryls and antioxidants may act as efficient free-radical scavengers and repair agents of specific-free-radical damage to biomolecules.4 On the basis of these properties and the effects they exhibit, therefore, these two classes of compounds are considered to play an important role in anticarcinogenesis and chemical protection from ionizing radiations.4 Their role in the * The author to whom the correspondence should be addressed. f This work is based on the Ph.D.

Associations between plasma antioxidants and hypertension in a community-based sample of 415 Australians aged 60–64

“…29 Uric acid is widely distributed in the body in relatively high concentrations and is an efficient scavenger of hydroxyl radicals, superoxides and singlet oxygen, and can chelate transition metals. 30 It contributes up to 60% of the TAC in healthy subjects. 31 Uric acid levels are frequently elevated in hypertensive patients, as was the case in our subjects.…”

Ürik Asidin Antioksidan ve Pro-Oksidan Özellikleri ile İlgili Kavram ve Tartışmalarının Derlemesi

“…Less is known about the beneficial effects of uric acid. Uric acid may function as a powerful antioxidant, and possibly one of the most important antioxidants in plasma [26][27][28] . Watanabe et al 23 has suggested that hyperuricemia maintains blood pressure during low salt intake environments, which may have provided a survival advantage during the course of primate evolution.…”

“…A negative prognostic factor for survival in heart failure patients is still controversial whether high uric acid is a compensatory attempt to counteract increased oxidative stress, an independent cause of CVD, or just a condition associated with other well-established risk factors such as hypertension, diabetes, and an accelerated clinical evolution of the disease [26][27][28][29] . Some authors suggested that high UA levels may promote the hypertensive organ damage, exerting a deleterious effect on endothelial function.…”

Improving meat quality through cattle feed enriched with mate extract: an integrated approach of the metabolic profile and redox chemistry of meat

“…168,169 Uric acid is an acid with a pK a1 value of 5.75 and a pK a2 of 9.8. Uric acid in plasma is mainly present as the urate monoanion 168,[170][171][172] and is considered to be the major antioxidant in human plasma. However, the low aqueous solubility of both uric acid and sodium urate carries a risk of precipitation of crystals of uric acid or sodium urate in tissue and joints.…”

“…179 Uric acid is generated in the gastrointestinal tract through the breakdown of purine bases from the diet. 169,170,174,183 Both serum and gastrointestinal levels of uric acid may thus be modulated by dietary factors and a high intake of red meat is traditionally considered a risk factor for hyperuricemia and diseases resulting from this condition. [174][175][176][177]184,185 A higher level of uric acid formed in the digestive tract during food digestion could, however, also have positive health effects, since uric acid could be important as a reductant of hypervalent meat pigments.…”